The objective of this Program Project is to study and develop multiple, new, synergistic strategies for intervention and rehabilitation after spinal cord injury. The research program is composed of two short-term and two long-term strategies which initially will be pursued independently, but ultimately will be combined to provide optimal synergistic effects. This powerful approach is based on recent advances in developing palliative strategies for spinal cord injury in several of our laboratories using state-of-the-art neurotransplantation, electrophysiological and molecular techniques. Herein, we combine a wealth of interdisciplinary experience focused on a series of interrelated projects, which promise to provide more effective, economical scientific contributions than if pursued separately. The short-term intervention section will address the issues of, 1) compensation of locomotor function using a novel prosthetic device, and 2) the reduction or prevention of muscle atrophy after spinal cord injury. The long-term intervention section will address the issues of, 3) optimizing functional integration of both fetal spinal cord implants and peripheral nerve grafts with the host tissue, and 4) designing intervention strategies based on the phenomenon of critical periods in development which allow functional recovery if damage occurs before, but not after, these specific time points. These four potent approaches have the potential not only for developing independent intervention methodologies, but also for designing a multifaceted approach to spinal cord injury. Therefore, studies are proposed to explore the effects of combining these strategies. We believe that the most desirable treatment strategies at some or all stages of intervention and rehabilitation after spinal cord injury ultimately may include electrical stimulation, neurotransplantation, exercise training and pharmacological modulation. Our team is in a unique and advanced position to lead the development of these strategies.